Comprehensive analysis of PPP4C's impact on prognosis, immune microenvironment, and immunotherapy response in lung adenocarcinoma using single-cell sequencing and multi-omics

被引:1
|
作者
Wang, Kaiyu [1 ]
Peng, Bo [1 ]
Xu, Ran [1 ]
Lu, Tong [2 ]
Chang, Xiaoyan [1 ]
Shen, Zhiping [1 ]
Shi, Jiaxin [1 ]
Li, Meifeng [1 ]
Wang, Chenghao [1 ]
Zhou, Xiang [1 ]
Xu, Chengyu [1 ]
Chang, Hao [3 ]
Zhang, Linyou [1 ]
机构
[1] Harbin Med Univ, Dept Thorac Surg, Affiliated Hosp 2, Harbin, Peoples R China
[2] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Thorac Surg, Sch Med, Shanghai, Peoples R China
[3] Harbin Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Harbin, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2024年 / 15卷
关键词
lung adenocarcinoma; PPP4C; immunotherapy; prognosis; single-cell; PROTEIN PHOSPHATASE 4; MOLECULAR CHARACTERISTICS; POOR-PROGNOSIS; EXPRESSION; NIVOLUMAB; BIOMARKER; PROMOTES; PROLIFERATION; THERAPY; BREAST;
D O I
10.3389/fimmu.2024.1416632
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background Elevated PPP4C expression has been associated with poor prognostic implications for patients suffering from lung adenocarcinoma (LUAD). The extent to which PPP4C affects immune cell infiltration in LUAD, as well as the importance of associated genes in clinical scenarios, still requires thorough investigation.Methods In our investigation, we leveraged both single-cell and comprehensive RNA sequencing data, sourced from LUAD patients, in our analysis. This study also integrated datasets of immune-related genes from InnateDB into the framework. Our expansive evaluation employed various analytical techniques; these included pinpointing differentially expressed genes, constructing WGCNA, implementing Cox proportional hazards models. We utilized these methods to investigate the gene expression profiles of PPP4C within the context of LUAD and to clarify its potential prognostic value for patients. Subsequent steps involved validating the observed enhancement of PPP4C expression in LUAD samples through a series of experimental approaches. The array comprised immunohistochemistry staining, Western blotting, quantitative PCR, and a collection of cell-based assays aimed at evaluating the influence of PPP4C on the proliferative and migratory activities of LUAD cells.Results In lung cancer, elevated expression levels of PPP4C were observed, correlating with poorer patient prognoses. Validation of increased PPP4C levels in LUAD specimens was achieved using immunohistochemical techniques. Experimental investigations have substantiated the role of PPP4C in facilitating cellular proliferation and migration in LUAD contexts. Furthermore, an association was identified between the expression of PPP4C and the infiltration of immune cells in these tumors. A prognostic framework, incorporating PPP4C and immune-related genes, was developed and recognized as an autonomous predictor of survival in individuals afflicted with LUAD. This prognostic tool has demonstrated considerable efficacy in forecasting patient survival and their response to immunotherapeutic interventions.Conclusion The involvement of PPP4C in LUAD is deeply intertwined with the tumor's immune microenvironment. PPP4C's over-expression is associated with negative clinical outcomes, promoting both tumor proliferation and spread. A prognostic framework based on PPP4C levels may effectively predict patient prognoses in LUAD, as well as the efficacy of immunotherapy strategy. This research sheds light on the mechanisms of immune interaction in LUAD and proposes a new strategy for treatment.
引用
收藏
页数:21
相关论文
共 45 条
  • [41] Single-cell and bulk RNA-sequence identified fibroblasts signature and CD8+T-cell - fibroblast subtype predicting prognosis and immune therapeutic response of bladder cancer, based on machine learning: bioinformatics multi-omics study
    Li, Jingxian
    Kong, Zheng
    Qi, Yuanjiong
    Wang, Wei
    Su, Qiang
    Huang, Wei
    Zhang, Zhihong
    Li, Shuai
    Du, E.
    INTERNATIONAL JOURNAL OF SURGERY, 2024, 110 (08) : 4911 - 4931
  • [42] Identification and validation of a novel signature based on immune-related genes from epithelial cells to predict prognosis and treatment response in patients with lung squamous cell cancer by integrated analysis of single-cell and bulk RNA sequencing
    Wu, Jiajun
    Li, Zhifeng
    Zhou, Weijun
    Hu, Zhuozheng
    Gao, Kun
    Yang, Jin
    Zhang, Wenxiong
    ONCOLOGY LETTERS, 2025, 29 (03)
  • [43] Identification of an antigen-presenting cells/T/NK cells-related gene signature to predict prognosis and CTSL to predict immunotherapeutic response for lung adenocarcinoma: an integrated analysis of bulk and single-cell RNA sequencing
    Huang, Liling
    Lou, Ning
    Xie, Tongji
    Tang, Le
    Han, Xiaohong
    Shi, Yuankai
    CANCER IMMUNOLOGY IMMUNOTHERAPY, 2023, 72 (10) : 3259 - 3277
  • [44] Identification of an antigen-presenting cells/T/NK cells-related gene signature to predict prognosis and CTSL to predict immunotherapeutic response for lung adenocarcinoma: an integrated analysis of bulk and single-cell RNA sequencing
    Liling Huang
    Ning Lou
    Tongji Xie
    Le Tang
    Xiaohong Han
    Yuankai Shi
    Cancer Immunology, Immunotherapy, 2023, 72 : 3259 - 3277
  • [45] Single-cell Multi-omics Analysis of Reactive Lymph Nodes, Affected Tissues, and Blood Reveals a Naive-like CD4+TRAIL+ T Cell Population That Differentially Directs Effector Anti-nuclear Antigen Reactive Responses in Patients with Sjogren's Syndrome and Systemic Sclerosis
    Papadimitriou, Theodoros Ioannis
    Singh, Prashant
    van Caam, Arjan
    Vonk, Madelon
    van der Horst-Bruinsma, Irene E.
    van der Kraan, Peter
    Aarntzen, Erik
    Huijnen, Martijn
    Koenen, Hans
    Thurlings, Rogier
    ARTHRITIS & RHEUMATOLOGY, 2024, 76 : 5146 - 5147